Applicant: Tracy L. Nelson, M.P.H., Ph.D., has a primary area of interest in the interaction of genetic and environmental factors in human disease, particularly obesity and type 2 diabetes mellitus. Her immediate goals are to learn the skills necessary to understand, analyze, and interpret human disease at the genotypic level taking into consideration the environmental context, with the ability to apply these skills to both population and family data. Her long-term career goal is to become an independent investigator by establishing an extramurally funded research program in this area. The NIDDK Mentored Research Scientist Development Award would provide the opportunity to receive the necessary training to achieve these goals. Research Development Plan: The research development plan Includes interactions and formal training with experts in all areas of the proposed project including the primary mentors, and advisory committee. The plan also includes formal course-work, participation in seminars, journal clubs, and attendance at scientific meetings. Overall, Dr. Nelson will learn a wide-variety of new skills in the genetic analysis of complex traits as well as basic laboratory techniques for genotyping. Research Project: The general aim of this research project is to study the joint effects of environmental risk factors and polymorphic candidate genes as determinants of obesity, obesity-related insulin resistance, and type 2 diabetes mellitus (T2DM). The overall objective is to increase understanding of the importance of the peroxisome proliferator activated receptor gamma (specifically the isoform 2 (PPARgamma2)) and peroxisome proliferator activated receptor gamma coactivator-1alpha (PGC-1alpha) by evaluating how variation in diet and physical activity modify PPARgamma2 and PGC-1alpha gene effects on weight gain, and development of obesity-related insulin resistance and T2DM in both Hispanics and non-Hispanic whites (NHW). These studies will be conducted using previously collected DNA and extensive longitudinal trait and risk factor data of the San Luis Valley Diabetes Study (SLVDS) a population-based cohort study as well as the nested San Luis Valley Family Study (SLVFS). Environment: Dr. Nelson will have an outstanding environment in which to carry out the proposed study, as well as, the necessary resources and support to successfully complete her training.